Microbial Delivery Vehicles for Allergens and Allergen-Derived Peptides in Immunotherapy of Allergic Diseases

Allergen-specific immunotherapy represents the only available curative approach to allergic diseases. The treatment has proven effective, but it requires repetitive administrations of allergen extracts over 3–5 years and is often associated with adverse events. This implies the need for novel therapeutic strategies with reduced side effects and decreased treatment time, which would improve patients’ compliance. Development of vaccines that are molecularly well defined and have improved safety profile in comparison to whole allergen extracts represents a promising approach. Molecular allergy vaccines are based on major allergen proteins or allergen-derived peptides. Often, such vaccines are associated with lower immunogenicity and stability and therefore require an appropriate delivery vehicle. In this respect, viruses, bacteria, and their protein components have been intensively studied for their adjuvant capacity. This article provides an overview of the microbial delivery vehicles that have been tested for use in allergy immunotherapy. We review in vitro and in vivo data on the immunomodulatory capacity of different microbial vehicles for allergens and allergen-derived peptides and evaluate their potential in development of allergy vaccines. We also discuss relevant aspects and challenges concerning the use of microbes and their components in immunotherapy of allergic diseases

Associations among different functional and structural arterial wall properties and their relations to traditional cardiovascular risk factors in healthy subjects: a cross-sectional study

BACKGROUND: The arterial wall possesses several functional and structural properties that define arterial health. Once they become impaired, cardiovascular risk increases. We aimed to ascertain the pattern of correlations among different arterial wall properties and to explore their relations to traditional risk factors and cardiovascular risk stratification. To allow such an investigation a middle-aged healthy population was recruited. METHODS: This cross-sectional study included 100 healthy males (aged 41.9 ± 6.4 years). Pulse wave velocity (PWV), β-stiffness and intima-media thickness (IMT) of the carotid artery, and brachial artery flow-mediated dilation (FMD) were measured by a standardized ultrasound approach. RESULTS: No correlation between FMD and IMT was found; only relatively poor correlations between PWV (or β-stiffness) and FMD existed, as well as between PWV (or β-stiffness) and IMT. PWV and β-stiffness highly correlated. Unexpectedly, only weak associations between PWV, β-stiffness, FMD, IMT and traditional risk factors were revealed. Hence, traditional risk factors (mainly age) explained only 10-50% of variability for PWV, β-stiffness, FMD and IMT. Although the subjects had low cardiovascular risk according to their Framingham score, their arterial wall properties were already impaired, particularly FMD. CONCLUSIONS: In healthy middle-age males we found: i) absent or poor correlations among arterial stiffness, IMT and endothelial function; ii) a low impact of traditional risk factors on the studied variables, and iii) the presence of impaired arterial wall properties despite low calculated cardiovascular risk. These results provide a deepened understanding of arterial wall properties and could help to improve cardiovascular risk stratification

Diabetična ketoacidoza: redek, a resen zaplet zdravljenja z zaviralci SGLT-2 – pregled literature in prikaz serije primerov

Zaviralci natrij-glukoznega koprenašalnega sistema-2 (SGLT-2) se vse pogosteje predpisujejo tako v diabetologiji kot tudi v drugih internističnih strokah. Primarno ugodno vplivajo na presnovne dejavnike, tj. parametre glikemije in na telesno maso. Poleg tega omogočajo zaščito tarčnih organov, srčno-žilnega sistema in ledvic, pri osebah s sladkorno boleznijo ali brez nje. Neželeni učinki ob zdravljenju z zaviralci SGLT-2 so redki, večinoma nenevarni in jih lahko preprečimo. Zelo redek, a življenje ogrožajoč zaplet je lahko pojav diabetične ketoacidoze. Dejavnikov, ki povečajo tveganje za njen nastanek, še niso popolnoma raziskali. V prispevku so opisani diabetična ketoacidoza in njene posebnosti ob zdravljenju z zaviralci SGLT-2 ter možni vzročni dejavniki zanjo. Poznavanje slednjih je predvsem pomembno zaradi možnosti aktivnega preprečevanja diabetične ketoacidoze. Najpogosteje se pojavi hkrati z zdravljenjem z zaviralci SGLT-2 ob okužbah, sladkorni bolezni tipa 1, opustitvi inzulinskega zdravljenja ter v primerih stradanja. Prispevek vključuje tudi prikaz serije primerov, ki so bili hospitalizirani na našem kliničnem oddelku zaradi diabetične ketoacidoze ob zdravljenju z zaviralci SGLT-2, ob različni sočasni antidiabetični terapiji

Thorough Clinical Evaluation of Skin, as well as Oral, Genital and Anal Mucosa is Beneficial in Lichen Planus Patients

Lichen planus (LP) is a common mucocutaneous disease of unknown aetiology with various geographical prevalence, may be related to some serious disorders such as squamous cell carcinoma and often remains underdiagnosed. The aim of this retrospective study was to thoroughly determine localization and clinical characteristics of LP lesions in a cohort of 173 Slovenian patients in association to the presence of accompanying symptoms and history of potential stressful events. Isolated cutaneous lesions of LP were found in 56.6% and isolated oral LP in 3.5% of patients. Thirty-four percent presented orocutaneous LP, whereas genitocutaneous LP was noted in 1.2%, orogenito-cutaneous LP in 4% and orogenital LP in 0.5% of patients. Underlying stressful events were noted in 36 out of 137 (26.3%) patients. Despite obviously visible localization of the lesions various medical specialists should be familiar with LP and thoroughly examine the complete skin, as well as oral, genital and anal mucosa in each LP patient to avoid a delay in diagnosing this disease and possibly disclose a much serious underlying condition. Psychological support should be offered, if needed

Thorough Clinical Evaluation of Skin, as well as Oral, Genital and Anal Mucosa is Beneficial in Lichen Planus Patients

Lichen planus (LP) is a common mucocutaneous disease of unknown aetiology with various geographical prevalence, may be related to some serious disorders such as squamous cell carcinoma and often remains underdiagnosed. The aim of this retrospective study was to thoroughly determine localization and clinical characteristics of LP lesions in a cohort of 173 Slovenian patients in association to the presence of accompanying symptoms and history of potential stressful events. Isolated cutaneous lesions of LP were found in 56.6% and isolated oral LP in 3.5% of patients. Thirty-four percent presented orocutaneous LP, whereas genitocutaneous LP was noted in 1.2%, orogenito-cutaneous LP in 4% and orogenital LP in 0.5% of patients. Underlying stressful events were noted in 36 out of 137 (26.3%) patients. Despite obviously visible localization of the lesions various medical specialists should be familiar with LP and thoroughly examine the complete skin, as well as oral, genital and anal mucosa in each LP patient to avoid a delay in diagnosing this disease and possibly disclose a much serious underlying condition. Psychological support should be offered, if needed

Problematika uživanja pijač z dodanim sladkorjem v Sloveniji in svetu

Pojavnost kardiometabolnih bolezni je dosegla pandemične razsežnosti, zato se čedalje večja pozornost posveča tudi z življenjskim slogom pogojenemu zdravju prebivalstva, še posebej načinu prehranjevanja in vnosu določenih skupin živil. Številne epidemiološke raziskave so dokazale, da je uživanje pijač z dodanim sladkorjem povezano z nastankom debelosti, sladkorne bolezni in srčno-žilnih bolezni, dodatno je tudi dober pokazatelj posameznikovega nezdravega življenjskega sloga. Pijače z dodanim sladkorjem so vir tako imenovanih »praznih kalorij«, ki nimajo hranilne vrednosti in predstavljajo največji dodatni vir energije in vnosa dodanih sladkorjev, še posebej fruktoze. Zmanjšanje vnosa pijač z dodanim sladkorjem dokazano vodi v znižanje telesne mase in zmanjšanje tveganja za nastanek kardiometabolnih bolezni. Uživanje pijač z dodanim sladkorjem je uvrščeno kar med 15 najpogostejših dejavnikov tveganja med kazalci nezdravega življenjskega sloga. Posledično je smiselno intenzivno ozaveščanje o pomembnosti opustitve uživanja pijač z dodanim sladkorjem, še posebej pri osebah s povečanim tveganjem za presnovne bolezni in mladih z nezdravim življenjskim slogom. V prispevku so opredeljene pijače z dodanim sladkorjem, opisana je njihova povezava z debelostjo, sladkorno boleznijo in srčno-žilnimi boleznimi ter možni zdravi nadomestki

Zaviralci SGLT-2

Zaviralci natrij-glukoznega prenašalnega sistema 2 (SGLT-2) so najnovejša skupina zdravil za zdravljenje sladkorne bolezni tipa 2, ki so v klinični uporabi zadnjih nekaj let. V proksimalnih tubulih ledvic zmanjšajo reabsorpcijo glukoze, ki se zato izloči z urinom. Zato se zniža koncentracija glukoze v krvi in nastopi ugodni vpliv na urejenost glikemije, obenem pa s tem ne povečajo tveganja za hipoglikemijo. Zaviralci SGLT-2 imajo tudi ugodne presnovne učinke, in sicer znižajo telesno maso, krvni tlak in koncentracijo sečne kisline v serumu. Upočasnijo tudi napredovanje začetne diabetične ledvične bolezni. Za nekatere predstavnike so tudi pokazali, da pomembno zmanjšujejo pojavnost srčno-žilnih dogodkov in zapletov, vendar mehanizem še ni v celoti raziskan in je predmet intenzivnega preučevanja. Redko povzročijo resne neželene učinke. V prispevku je opisan mehanizem delovanja zaviralcev SGLT-2, njihov vpliv na urejenost glikemije in drugo: presnovni učinki, vpliv na pojavnost srčno-žilnih bolezni in najpogostejši neželeni učinki ter možnosti predpisovanja zaviralcev SGLT-2 v Sloveniji